p120RasGAP SH3 domain in complex with DLC1 RhoGAP domainp120RasGAP SH3 domain in complex with DLC1 RhoGAP domain

Structural highlights

7tpb is a 8 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3.2Å
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

B4DTL8_HUMAN

Publication Abstract from PubMed

RhoGAP proteins are key regulators of Rho family GTPases and influence a variety of cellular processes, including cell migration, adhesion, and cytokinesis. These GTPase activating proteins (GAPs) downregulate Rho signaling by binding and enhancing the intrinsic GTPase activity of Rho proteins. Deleted in liver cancer 1 (DLC1) is a tumor suppressor and ubiquitously expressed RhoGAP protein; its activity is regulated in part by binding p120RasGAP, a GAP protein for the Ras GTPases. In this study, we report the co-crystal structure of the p120RasGAP SH3 domain bound directly to DLC1 RhoGAP, at a site partially overlapping the RhoA binding site and impinging on the catalytic arginine finger. We demonstrate biochemically that mutation of this interface relieves inhibition of RhoGAP activity by the SH3 domain. These results reveal the mechanism for inhibition of DLC1 RhoGAP activity by p120RasGAP and demonstrate the molecular basis for direct SH3 domain modulation of GAP activity.

SH3 domain regulation of RhoGAP activity: Crosstalk between p120RasGAP and DLC1 RhoGAP.,Chau JE, Vish KJ, Boggon TJ, Stiegler AL Nat Commun. 2022 Aug 15;13(1):4788. doi: 10.1038/s41467-022-32541-4. PMID:35970859[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Chau JE, Vish KJ, Boggon TJ, Stiegler AL. SH3 domain regulation of RhoGAP activity: Crosstalk between p120RasGAP and DLC1 RhoGAP. Nat Commun. 2022 Aug 15;13(1):4788. doi: 10.1038/s41467-022-32541-4. PMID:35970859 doi:http://dx.doi.org/10.1038/s41467-022-32541-4

7tpb, resolution 3.20Å

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